The major goal of the proposed research is the analysis of the process of reverse transcription by RLV DNA polymerase, through continuing biochemical investigation both in vitro and in vivo. Emphasis will be placed on the process of DNA synthesis directed by virion genomic 70S RNA, and the possible role(s) of viral and cellular proteins in maximizing the efficiency of that synthesis. The enzymological studies to be carried out will explore the mechanism of inhibition of RLV DNA polymerase and its associated RNase H activity by inorganic phosphate. The possible role of cellular and/or DNA polymerase-associated RNase H in the sunthesis of proviral DNA will be investigated, as well as the mechansistic interrelationship of the synthetic and nucleolytic activities associated with the RLA DNA polymerase. We also intend to fully chracterize the high molecular weight intracytosplasmic form of RLV DNA polymerase, and to determine whether it is present in an in vivo MuLV-synthesizing system such as the AKR mouse thymus.